Related Experiment Video
Updated: Dec 30, 2025
The Soft Agar Colony Formation Assay
Published on: October 27, 2014
Down-regulation of SLC35C1 induces colon cancer through over-activating Wnt pathway
Minzi Deng1,2, Zhihong Chen3, Jieqiong Tan4
1Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, China.
Abstract:
The canonical Wnt signalling pathway is a critical pathway involved in the proliferation of cells. It has been well-established that it plays the central role during colorectal carcinogenesis and development. Yet the exact molecular mechanism of how the canonical Wnt pathway is fine-tuned remains elusive. We found that SLC35C1, a GDP-fucose transporter, negatively regulates the Wnt signalling pathway. We show here that SLC35C1 is reduced in all colon cancer by both immunohistochemistry images and TCGA data, whereas β-catenin is increased. Down-regulation of SLC35C1 is also detected by real-time PCR in stage 3 and stage 4 colorectal cancer tissues. Moreover, analysing the TCGA database with cBioPortal reveals the negative correlation of SLC35C1 mRNA level to the expression of β-catenin. Reduced SLC35C1 significantly promotes cell proliferation and colony formation of HEK293 cells. Meanwhile, in HEK293 cells silencing SLC35C1 activates canonical Wnt pathway, whereas overexpressing SLC35C1 inhibits it. Consistently, the reduction of SLC35C1 in HEK293 cells also elevated the mRNA level of Wnt target genes C-myc, Axin2 and Cyclin D1, as well as the secretion of Wnt3a. In conclusion, we identified SLC35C1 as a negative regulator of the Wnt signalling pathway in colon cancer. Decreased SLC35C1 may cause over-activation of Wnt signalling in colorectal cancer.
Insights
The GDP-fucose transporter SLC35C1 negatively regulates the Wnt signalling pathway. Reduced SLC35C1 levels in colon cancer correlate with increased cell proliferation and Wnt pathway activation.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- The canonical Wnt signalling pathway is crucial for cell proliferation and plays a central role in colorectal cancer development.
- The precise molecular mechanisms fine-tuning Wnt pathway activity remain incompletely understood.
Purpose of the Study:
- To investigate the role of SLC35C1 (GDP-fucose transporter) in regulating the canonical Wnt signalling pathway.
- To determine the impact of SLC35C1 expression levels on colorectal cancer cell proliferation and Wnt pathway activity.
Main Methods:
- Immunohistochemistry and TCGA data analysis to assess SLC35C1 and β-catenin expression in colon cancer tissues.
- Real-time PCR to detect SLC35C1 down-regulation in stage 3 and 4 colorectal cancer.
- Functional studies in HEK293 cells involving SLC35C1 silencing and overexpression.
- Analysis of Wnt target gene expression (C-myc, Axin2, Cyclin D1) and Wnt3a secretion.
Main Results:
- SLC35C1 expression is reduced in all examined colon cancers, inversely correlating with β-catenin levels.
- Down-regulation of SLC35C1 was observed in advanced stage colorectal cancer tissues.
- Reduced SLC35C1 expression significantly enhances HEK293 cell proliferation and colony formation.
- Silencing SLC35C1 activates the canonical Wnt pathway, increasing Wnt target gene expression and Wnt3a secretion, while overexpression inhibits it.
Conclusions:
- SLC35C1 acts as a negative regulator of the Wnt signalling pathway in colon cancer.
- Decreased SLC35C1 expression contributes to the over-activation of Wnt signalling observed in colorectal cancer.
Related Concept Videos
02:54Canonical Wnt Signaling Pathway
01:41Non-Canonical Wnt Signaling Pathways
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
01:33Pleiotropy